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The immunological and virological consequences of planned treatment interruptions in children with HIV infection

Authors :
Klein, Nigel
Sefe, Delali
Mosconi, Ilaria
Zanchetta, Marisa
Castro, Hannah
Jacobsen, Marianne
Jones, Hannah
Bernardi, Stefania
Pillay, Deenan
Giaquinto, Carlo
Walker, A. Sarah
Gibb, Diana M.
De Rossi, Anita
Paediatric, European Network for Treatment of AIDS 11 Trial Team including Aboulker JP
Ananworanich, J
Babiker, A
Belfrage, E
Bernardi, S
Blanche, S
Bohlin, Ab
Bologna, R
Burger, Dm
Butler, K
Castelli Gattinara, G
Castro, H
Clayden, P
Compagnucci, A
Darbyshire, Jh
Debré, M
Faye, A
de Groot, R
della Negra, M
Duiculescu, D
Giaquinto, C
Gibb, Dm
Grosch Wörner, I
Hainault, M
Harper, L
Klein, N
Lallemant, M
Levy, J
Lyall, H
Marczynska, M
Mardarescu, M
Mellado Peña, Mj
Nadal, D
Niehues, T
Peckham, C
Pillay, D
Ramos Amador, Jt
Rosado, L
Rosso, R
Rudin, C
Saidi, Y
Scherpbier, Hj
Sharland, M
Stevanovic, M
Thorne, C
Tovo, Pier Angelo
Tudor Williams, G
Valerius, N
Walker, As
Welch, S
Wintergerst, U
Aboulker, Jp
Mofenson, L
Moye, J
Saïdi, Y
Cressey, Tr
Jacqz Aigrain, E
Khoo, S
Tréluyer, Jm
De Rossi, A
Ngo Giang Huong, N
Muñoz Fernandez, Ma
Hill, C
Lepage, P
Pozniak, A
Vella, S
Hadjou, G
Léonardo, S
Riault, Y
Buck, L
Farrelly, L
Forcat, S
Harrison, L
Horton, J
Johnson, D
Moore, S
Taylor, C
Chalermpantmetagul, S
Peongjakta, R
Chailert, S
Fregonese, F
Jourdain, G
Butler, D
Carlton, C
Collins, D
Kao, G
Van Buskirk, S
Watson, S
Corradini, S
Floret, D
Le Thi, Tt
Monpoux, F
Cottalorda, J
Lefebvre, Jc
Mellul, S
Boudjoudi, N
Firtion, G
Denon, M
Picard, F
Beniken, D
Damond, F
Alexandre, G
Tricoire, J
Nicot, F
Krivine, A
Rivaux, D
Chaix, Ml
Notheis, G
Strotmann, G
Schlieben, S
Rampon, O
Zanchetta, M
Ginocchio, F
Viscoli, C
Martino, A
Pontrelli, G
Concato, C
Mazza, A
Rossetti, G
Dobosz, S
Oldakowska, A
Popielska, J
Kaflik, M
Stanczak, J
Stanczack, G
Dyda, T
González Tomé, Mi
Delgado García, R
Fernandez Gonzalez, Mt
Martín Fontelos, P
Piñeiro Pérez, R
Penin, M
Garcia Mellado, I
Medina, Af
Ascencion, B
Garcia Bermejo, I
Garcia Vela, Ja
Martin Rubio, I
Gurbindo, D
Navarro Gomez, Ml
Jimenez, Jl
Garcia Torre, A
José Gómez, Mi
García Rodriguez, Mc
Moreno Pérez, D
Núñez Cuadros, E
Asensi Botet, F
Pérez, A
Pérez Tamarit, Md
Gobernado Serrano, M
Gonzales Molina, A
Kalhert, C
Dobrovoljac, M
Berger, C
Nobile, G
Reinhard, S
Schupbach, J
Bunupuradah, T
Puthanakit, T
Pancharoen, C
Butterworth, O
Phasomsap, C
Jupimai, T
Ubolyam, S
Phanuphak, P
Mai, C
Kanjanavanit, S
Namwong, T
Chutima, D
Raksasang, M
Foster, C
Hamadache, D
Campbell, S
Newbould, C
Monrose, C
Patel, D
Kaye, S
Seery, P
Wildfire, A
Novelli, V
Shingadia, D
Moshal, K
Flynn, J
Clapson, M
Allen, A
Spencer, L
Depala, M
Jacobsen, M
Mcmaster, P
Phipps, M
Orendi, J
Farmer, C
Liebeschuetz, S
Sodeinde, O
Wong, S
Heath, Y
Scott, S
Gandhi, K
Lewis, P
Daglish, J
Weiner, L
Famiglietti, M
Rana, S
Yu, P
Roa, J
Puga, A
Haerry, A
Inma, A.
Source :
PLoS ONE; Vol 8, PLoS ONE, PLoS One, 8, 10, PLoS ONE, Vol 8, Iss 10, p e76582 (2013), PLoS One, 8
Publication Year :
2013
Publisher :
San Francisco, CA : Public Library of Science, 2013.

Abstract

Contains fulltext : 126098.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To evaluate the immunological and viral consequences of planned treatment interruptions (PTI) in children with HIV. DESIGN: This was an immunological and virological sub-study of the Paediatric European Network for Treatment of AIDS (PENTA) 11 trial, which compared CD4-guided PTI of antiretroviral therapy (ART) with continuous therapy (CT) in children. METHODS: HIV-1 RNA and lymphocyte subsets, including CD4 and CD8 cells, were quantified on fresh samples collected during the study; CD45RA, CD45RO and CD31 subpopulations were evaluated in some centres. For 36 (18 PTI, 18 CT) children, immunophenotyping was performed and cell-associated HIV-1 DNA analysed on stored samples to 48 weeks. RESULTS: In the PTI group, CD4 cell count fell rapidly in the first 12 weeks off ART, with decreases in both naive and memory cells. However, the proportion of CD4 cells expressing CD45RA and CD45RO remained constant in both groups. The increase in CD8 cells in the first 12 weeks off ART in the PTI group was predominantly due to increases in RO-expressing cells. PTI was associated with a rapid and sustained increase in CD4 cells expressing Ki67 and HLA-DR, and increased levels of HIV-1 DNA. CONCLUSIONS: PTI in children is associated with rapid changes in CD4 and CD8 cells, likely due to increased cell turnover and immune activation. However, children off treatment may be able to maintain stable levels of naive CD4 cells, at least in proportion to the memory cell pool, which may in part explain the observed excellent CD4 cell recovery with re-introduction of ART.

Details

Language :
English
ISSN :
19326203
Database :
OpenAIRE
Journal :
PLoS ONE; Vol 8, PLoS ONE, PLoS One, 8, 10, PLoS ONE, Vol 8, Iss 10, p e76582 (2013), PLoS One, 8
Accession number :
edsair.doi.dedup.....751679ec2c5c90ec90c289bbb4050274